Abstract Objective: Agomelatine (AGM), an antidepressant drug has low biological half-life coupled with extensive hepatic first-pass metabolism. For effective treatment of depression, daily medication is required but irregular dose intake occurs due to psychological illness which can be overcome by development of transdermal drug delivery system. But for effective transdermal delivery permeation of AGM through stratum corneum is a crucial step. Thus present study was intended to formulate and optimize polymeric nanoparticles of agomelatine and to compare the effect of binary combinations of solvent system on permeability profiling of pure agomelatine with statistically optimized polymeric nanoparticles. Methods: Polymeric agomelatine nanoparticles (AGM-PNPs) were prepared by nano-precipitation method which was further optimized by experimental design and characterized by FTIR, DSC, XRD and SEM study while ex-vivo study was performed on adult male wistar rats. Results: The optimized formulation has particle size in nano range (107.64 nm) with low PDI (0.209), stable zeta potential (−15 mV) and high entrapment efficiency (81.91%). Ex-vivo analysis of optimized nanoparticles suggests that nanoparticles permeate faster compared to plain AGM, while, permeation profile of AGM was enhanced when combination of solvent systems were used. It was observed that among various solvent system 33% PG-ethanol showed maximum flux (148.48 ± 3.24 µg/cm2/h) and least lag time (4.04 ± 0.12 h). The flux was further enhanced (180.98 ± 2.54 µg/cm2/h) when 5%v/v transcutol-HP was added as penetration enhancer. Conclusion: The above observations concluded that binary combination of 33% PG-ethanol with 5 %v/v transcutol-HP can serve as a solvent system of choice for effective transdermal delivery of agomelatine via nanoparticulate system.

中文翻译：

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溶剂系统二元组合对纯阿戈美拉汀在大鼠皮肤渗透性分析的影响：与统计优化的聚合物纳米粒子的比较研究

摘要 目的：阿戈美拉汀（AGM）是一种抗抑郁药，生物半衰期短，肝脏首过代谢广泛。为了有效治疗抑郁症，需要每天服药，但由于心理疾病会出现不规律的剂量摄入，这可以通过开发透皮给药系统来克服。但是对于通过角质层的AGM的有效透皮递送是关键步骤。因此，本研究旨在配制和优化阿戈美拉汀的聚合物纳米粒子，并比较溶剂系统的二元组合对纯阿戈美拉汀的渗透性曲线与统计优化的聚合物纳米粒子的影响。方法：采用纳米沉淀法制备聚合物阿戈美拉汀纳米粒子（AGM-PNPs），并通过实验设计进一步优化，并通过FTIR、DSC、XRD和SEM研究对其进行表征，同时对成年雄性wistar大鼠进行离体研究。结果：优化后的配方粒径在纳米级（107.64 nm），PDI低（0.209），zeta电位稳定（-15 mV），包封率高（81.91%）。优化纳米粒子的离体分析表明，与普通 AGM 相比，纳米粒子的渗透速度更快，而当使用溶剂系统组合时，AGM 的渗透曲线得到增强。据观察，在各种溶剂系统中，33% PG-乙醇显示出最大通量（148.48 ± 3.24 µg/cm2/h）和最小滞后时间（4.04 ± 0.12 h）。通量进一步增强 (180.98 ± 2. 54 µg/cm2/h) 当 5%v/v transcutol-HP 添加作为渗透促进剂时。结论：上述观察得出结论，33% PG-乙醇与 5%v/v transcutol-HP 的二元组合可作为通过纳米颗粒系统有效透皮递送阿戈美拉汀的溶剂系统的选择。